Epilepsy is a neurological disease characterized by recurrent seizures that can lead to uncontrollable muscle twitching, changes in sensitivity to sensory perceptions, and disorders of consciousness. Although modern medicine has effective antiepileptic drugs, the need for accessible and cost-effective medication is urgent, and products derived from plants could offer a solution.
Compound | Effective Dose | Animal Model | Seizure-Inducing Agent | Mechanism | Source |
---|---|---|---|---|---|
Paeoniflorin (monoterpene) | 100 mg/kg/day, p.o. (for 10 days) |
Male immature Lewis rats | Hyperthermia | Suppression of [Ca2+]i elevation via mGluR5 | [42][16] |
Thymol (monoterpene) | 50 and 100 mg/kg, i.p. | Male Swiss mice Male Wistar rats |
PTZ, MES, Strychnine, 4-AP | Possibly via positive modulation of GABAA and voltage-dependent Na+ channel blockade | [43][17] |
Iritectol G (triterpene) | 10 μM | Neocortical neurons of C57BL/6 mice | 4-AP | Interaction with inactivated state of VGSC | [44][18] |
Imperatorin (coumarin) | 30–50 µM | NG108-15 cells | Voltage-clamp assay | Inhibition of VGSC | [45][19] |
Xanthotoxin (coumarin) | 50 and 100 mg/kg, i.p. + CBZ 100 mg/kg, i.p. + VPA |
Male Swiss mice | MES | Inhibition of P-glycoprotein Inhibition of VGPC Modulation of calcium-dependent potassium channels |
[46][20] |
Acacetin (flavonoid) |
10 and 50 mg/kg, i.p. | Male Sprague Dawley rats | KA | Inhibition of glutamate release by decrease in voltage-dependent Ca2+ entry | [47][21] |
Aconitine (alkaloid) |
1 μM | Hippocampal slices of male Wistar rats | Low Mg2+-ACSF | Modulation of Na+ channels | [29][3] |
Compound | Effective Dose | Animal Model | Seizure-Inducing Agent | Mechanism | Source |
---|---|---|---|---|---|
Thymol (monoterpene) | 50 and 100 mg/kg, i.p. | Male Swiss mice Male Wistar rats |
PTZ, MES, Strychnine, 4-AP | Possibly via positive modulation of GABAA and voltage-dependent Na+ channel blockade | [43][17] |
Thymoquinone (monoterpene) | 40 mg/kg/day, p.o. (for 7 days) |
Sprague Dawley rats | PTZ | Activation of GABAB1R/CaMKII/pCREB pathway | [55][29] |
Paederosidic acid (iridoid) | 5–40 mg/kg, i.p. | Male ICR mice Sprague Dawley rats |
MES PTZ |
Upregulation of GAD65 | [59][33] |
Valepotriate (iridoid) | 5–20 mg/kg/day, i.p. (for 3 weeks) |
Male ICR mice Sprague Dawley rats |
MES PTZ |
Upregulation of GABAA, GAD65, and Bcl-2 and downregulation of caspase-3 | [58][32] |
Bilobalide (sesquiterpene) | 30 mg/kg/day, p.o. (for 4 days) |
Hippocampus, cortex, and striatum of male ddY mice | INH | Elevation of GABA levels Potentiation of GAD activity |
[61][35] |
Curcumol (sesquiterpene) | 100 mg/kg/day, i.p. (for 3 days) |
Male C57BL/6J mice | PTZ KA |
Facilitation of GABAergic inhibition | [73][47] |
(+)-Dehydrofukinone (sesquiterpene) | 10, 30, and 100 mg/kg, i.p. | Female Swiss mice | PTZ | Modulation of GABAA receptors | [74][48] |
3-Acetylaconitine (alkaloid) | 0.01–1 μM | Hippocampal slices of male Wistar rats | Mg2+-free ACSF Bicuculline |
Inactivation of Na+ channels | |
Betulin (triterpene) | [ | 31 | ] | [ | 5] |
Lappaconitine (alkaloid) | 1–100 μM | Hippocampal slices of male Wistar rats | Low Mg2+-ACSF Bicuculline |
Blockade of Na+ channels | [32][6] |
N-desacetyl lappaconitine (alkaloid) | 1–100 μM | Hippocampal slices of male Wistar rats | Low Mg2+-ACSF Bicuculline |
Blockade of Na+ channels | [32][6] |
1-Benzoylnapelline (alkaloid) | 1–100 μM | Hippocampal slices of male Wistar rats | Low Mg2+-ACSF Bicuculline |
Modulation of Na+ channels | [33][7] |
6-Benzoylheteratisine (alkaloid) | 0.01–10 μM | Hippocampal slices of male Wistar rats | Bicuculline | Blockade of Na+ channels | [34][8] |
Nantenine (alkaloid) |
20–50 mg/kg, i.p. | Male albino mice | PTZ MES |
Decrease in Ca2+-influx into the cell | [48][22] |
Piperine (alkaloid) |
5, 10, and 20 mg/kg, i.p. | Male Swiss mice | PTZ, MES, NMDA, PTX, Bicuculline, BAYK-8644, Strychnine | Na+ channel antagonist activity | [35][9] |
Veratridine (alkaloid) |
1 μM | Hippocampal slices of male Wistar rats | Low Ca2+/high Mg2+-ACSF | Block of inactivation of Na+ channels | [30][4] |
50 and 100 mg/kg, i.p. | |||||
Male ICR mice | |||||
Bicuculline | |||||
Binding to the GABA | |||||
A | |||||
receptor | [ | 75 | ] | [ | 49] |
Ginsenoside Rg3 (triterpene) | 100 μM | Xenopus laevis oocytes | Electrode voltage-clamp technique | GABAA receptor activation via interaction with the γ2 subunit | [76][50] |
Ursolic acid stearoyl glucoside (triterpene) | 50 mg/kg, i.p. | Wistar albino rats | MES INH |
Possibly via GABA receptor stimulation | [77][51] |
Embelin (benzoquinone) | 0.156–0.625 mg/kg, i.p. | Adult zebrafish | PTZ | Affinity toward GABAA receptor | [78][52] |
Cnidilin (coumarin) |
300 µM | Xenopus oocytes | Two-microelectrode voltage clamp assay | Modulation of GABAA receptors of the subunit combination α1β2γ2S | [79][53] |
Osthole (coumarin) |
300 µM | Xenopus oocytes | Two-microelectrode voltage clamp assay | Modulation of GABAA receptors of the subunit combination α1β2γ2S | [79][53] |
Lucidafuranocouma-rin A (coumarin) | 10–16 μM | Zebrafish larvae | PTZ | Possibly via interaction with the GABAA receptor | [68][42] |
Oxypeucedanin (coumarin) | 10–40 μM | Zebrafish larvae | PTZ | Possibly via interaction with the GABAA receptor | [69][43] |
Oxypeucedanin hydrate (coumarin) | 20–50 μM | Zebrafish larvae | PTZ | Possibly via interaction with the GABAA receptor | [69][43] |
Notopterol (coumarin) | 0.25–2 μM | Zebrafish larvae | PTZ | Possibly via interaction with the GABAA receptor | [69][43] |
Pimpinellin (coumarin) | 20–80 μM | Zebrafish larvae | PTZ | Possibly via interaction with the GABAA receptor | [69][43] |
Hyuganin C (coumarin) | 2.5–20 μM | Zebrafish larvae | PTZ | Possibly via interaction with the GABAA receptor | [69][43] |
Rosmarinic acid (phenolic) |
30 mg/kg, i.p. | Female C57BL/6 mice | PTZ Pilocarpine |
Probably activation of the GABAergic system | [80][54] |
Chlorogenic acid (phenolic) |
5 mg/kg/day, p.o. (for 15 days) |
Male Swiss albino mice | Pilocarpine | Suppressing glutamate receptors, neuroprotective effect | [81][55] |
Gastrodin (phenolic) |
60 mg/kg/day, p.o. (for 7 days) |
Mongolian gerbils | Genetic seizure model (seizure-sensitive gerbils) | Decrease in GABA degradation Decrease in GABA-T, SSADH, and SSAR immunoreactivities |
[82][56] |
Rutin (flavonoid) |
50 and 150 nM, i.c.v. | Male Wistar rats | PTZ | Positive allosteric modulation of the GABAA receptor complex via interaction at the benzodiazepine site | [83][57] |
Wogonin (flavonoid) |
5 and 10 mg/kg, i.p. | Male Sprague Dawley rats | MES PTZ |
Potentiation of the activity of GABA | [84][58] |
Vitexin (flavonoid) |
100 and 200 µM, i.c.v. | Male Wistar rats | PTZ | Interaction with GABAA benzodiazepine receptor complex | [85][59] |
10 mg/kg/day, p.o. (for 15 days) |
Male Swiss albino mice | Pilocarpine | Suppressing glutamate receptors, neuroprotective effect | [81][55] | |
Nobiletin (flavonoid) |
12.5, 25, and 50 mg/kg/day, o.g. (for 6 days) |
C57BL/6 mice | PTZ | Modulation GAD65/GABAA expression, BDNF-TrkB, PI3K/Akt | [86][60] |
(+)-Erythravine (alkaloid) | 0.25–3 μg/μL, i.c.v. | Male Wistar rats | Bicuculline, NMDA, KA, PTZ | Probably modifying GABA neurotransmission | [87][61] |
(+)-11-α-Hydroxy-erythravine (alkaloid) | 0.25–3 μg/μL, i.c.v. | Male Wistar rats | Bicuculline, NMDA, KA, PTZ | Probably modifying GABA neurotransmission | [87][61] |
Huperzine A (alkaloid) | 0.6 mg/kg, i.p. | Male Sprague Dawley rats | PTZ | Activation of cortical GABA transmission | [66][40] |
Lobeline (alkaloid) |
10, 20, 30 mg/kg, i.p. | Male Swiss mice | PTZ Strychnine |
Enhancing the GABA release | [88][62] |
Montanine (alkaloid) |
30 and 60 mg/kg, i.p. | Swiss mice and Wistar rats of either sex | PTZ | Modulation of several neurotransmitter receptor systems including GABAA receptors | [89][63] |
Piperine (alkaloid) |
2.5, 5, 10, and 20 mg/kg, i.p. | Male Swiss mice | Pilocarpine | Multiple anticonvulsant mechanisms, modulation of the GABA system, antioxidant, and anti-inflammatory activity | [90][64] |